Kcnh2 Conditional Knockout mouse models

Kcnh2, the mouse ortholog of human KCNH2, encodes Kv11.1 (ERG1), a voltage-gated potassium channel with an amino-terminal PAS domain and a carboxy-terminal cyclic nucleotide-binding homology domain that interact to set unusually slow deactivation alongside very fast, voltage-dependent C-type inactivation. This gating signature makes ERG1 the carrier of the cardiac rapid delayed rectifier that terminates the action potential plateau, and the same channel regulates firing frequency and spike-frequency adaptation in brain, where KCNH2 variants have been tied to schizophrenia-associated isoforms. Loss-of-function KCNH2 mutations cause long QT syndrome type 2 and the promiscuous inner-cavity binding pocket makes ERG1 the central off-target in drug safety testing. Because mouse ventricular repolarization relies less on this current, humanized knockin alleles that replace the pore and cavity residues are usually more informative than deletion for proarrhythmia work, while conditional nulls address neuronal excitability. Kcnh6 and Kcnh7 form heteromeric ERG channels, so subunit composition should be measured directly.

Kcnh2 conditional knockout mice carry a floxed allele so you delete function only where Cre is active. The germline allele stays intact until you cross to a tissue specific Cre. Labs reach for this design when a global knockout is lethal, when they need adult onset loss, or when regional redundancy hides a whole body phenotype.